5npp | pdb_00005npp

2.22A STRUCTURE OF THIOPHENE2 AND GSK945237 WITH S.AUREUS DNA GYRASE AND DNA

spinqualitylabelsall models 5npp, resolution 2.22Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5npp is a 6 chain structure with sequence from Staphylococcus aureus subsp. aureus N315 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.22Å Ligands: 6EJ, 94K, DMS, GOL, MN, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GYRA_STAAN DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.[HAMAP-Rule:MF_01897]GYRB_STAAN DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings (By similarity). Publication Abstract from PubMed A paucity of novel acting antibacterials is in development to treat the rising threat of antimicrobial resistance, particularly in Gram-negative hospital pathogens, which has led to renewed efforts in antibiotic drug discovery. Fluoroquinolones are broad-spectrum antibacterials that target DNA gyrase by stabilizing DNA-cleavage complexes, but their clinical utility has been compromised by resistance. We have identified a class of antibacterial thiophenes that target DNA gyrase with a unique mechanism of action and have activity against a range of bacterial pathogens, including strains resistant to fluoroquinolones. Although fluoroquinolones stabilize double-stranded DNA breaks, the antibacterial thiophenes stabilize gyrase-mediated DNA-cleavage complexes in either one DNA strand or both DNA strands. X-ray crystallography of DNA gyrase-DNA complexes shows the compounds binding to a protein pocket between the winged helix domain and topoisomerase-primase domain, remote from the DNA. Mutations of conserved residues around this pocket affect activity of the thiophene inhibitors, consistent with allosteric inhibition of DNA gyrase. This druggable pocket provides potentially complementary opportunities for targeting bacterial topoisomerases for antibiotic development. Thiophene antibacterials that allosterically stabilize DNA-cleavage complexes with DNA gyrase.,Chan PF, Germe T, Bax BD, Huang J, Thalji RK, Bacque E, Checchia A, Chen D, Cui H, Ding X, Ingraham K, McCloskey L, Raha K, Srikannathasan V, Maxwell A, Stavenger RA Proc Natl Acad Sci U S A. 2017 May 30;114(22):E4492-E4500. doi:, 10.1073/pnas.1700721114. Epub 2017 May 15. PMID:28507124 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Gyrase 3D Structures

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